Areas To Seal
The easiest answer to the question of where to seal air distribution systems is "just about everywhere." Here are the key locations to be sealed, in order of priority:
Disconnected components, including tears in flex duct, and strained connections between ductwork.
All seams in the air handling unit. Also seal the holes in the air handling unit for the refrigerant, thermostat and condensate lines. Use tape rather than mastic to seal between the seams in the panels of the air handling unit so they can be easily removed during maintenance.
The connections between the air handling unit and the supply and return plenums. After the air handling unit, the supply and return plenums have the greatest pressure, so even small holes result in large leaks. Remove insulation if necessary and seal all corners and connections.
The return and supply trunk lines, takeoffs, elbows, and other connections.